Jan. 09, 2015

Sifting Soils for New Approaches to Antibiotics

IRA FLATOW: This is "Science Friday." I'm Ira Flatow. Most of the antibiotics we use, today, weren't just dreamed up from nothing. They were discovered somewhere in nature, part of a natural arms race between species of microbes.

First, there was Fleming and penicillin mold, of course, but then a wave of antibiotics that came from bacteria living in the soil. In more recent years, as that well has run dry, researchers have tried designing antibiotics from the ground up, in the lab. That's only been limited, only had a limited success because the bacteria have evolved a resistance to many of the antibiotics on the market.

Going back to the future, scientists have returned to the soil to see if they can find new hope among the 99% of bacteria that refuse to grow in the laboratory. It's an incredible number. You can't grow 99% of the bacteria in a laboratory.

But we now have some hope because they have succeeded in at least one. According to the journal Nature, they've come up with a way to grow some of those unculturable soil bacteria. And when they did, they found what might be the first-- an entirely new class of antibiotics, one that even works against some of the drug resistant strains out there.

Joining me now, to talk about it, is Kim Lewis. He's one of the authors of the report. He's a professor and director of the Antimicrobial Discovery Center at Northeastern University, in Boston. Welcome to the program.

KIM LEWIS: Thanks for having me.

IRA FLATOW: You've been working on this idea for years. Have you not?

KIM LEWIS: Yes. That's true.

IRA FLATOW: And basically, describe what you did. To me, it almost looked like planting tomato seeds in egg shell crates.

KIM LEWIS: It is actually very similar to that. So with my collaborator, Slava Epstein here at Northeastern, we were wondering, how could we figure out a way to grow uncultured bacteria. And it became obvious to us that we're not going to succeed if we continue tinkering with growth media in our Petri dishes because that hasn't worked.

Then we decided that, how about we try growing them in their natural environment, where, of course, they do grow? So we came up with a simple gadget to do that. The gadget is a diffusion chamber.

We take a sample from soil and dilute mix with agar. And instead of pouring it into the Petri dish, we sandwich it between two semipermeable membranes, which then get glued onto an O-ring. And that contraption goes back into the soil.

So now everything diffuses through that chamber. And bacteria get their nutrients and growth factors from the natural environment. And they grow. So essentially, we trick them. They don't know that something happened to them.

IRA FLATOW: And so they grow into a colony which you can, then, take into the lab in a Petri dish.

KIM LEWIS: Yes. Exactly. What we discovered is that once a colony is formed, then, with a high probability, it will become domesticated and will grow in the lab.

IRA FLATOW: Mhm. And what were you able to-- one in particular, one-- you grew 10,000 of these. Right? And you've found one that was exceptional.

KIM LEWIS: Yes. So this is a collaboration, I must say, with NovoBiotic, a startup company here in Cambridge, that is using this technology and collaborating with us. And so, from that collection of strains, we found, of course, a number of bacteria that produce antibiotics. But one was particularly interesting.

It was only distantly related to known organisms. It was unusual in the number of features and was making a potent compound. But there was one very striking feature of that compound that we did not anticipate, did not expect at all. We could not find any resistance to this compound, in the pathogens we tested it against.

IRA FLATOW: Mhm. And this new method, it holds a potential for discovering many, many more antibiotics?

KIM LEWIS: Yes. Of course. So the culture collection that NovoBiotic put together, so far, is 50,000 isolates. From that number, we discovered 25 new antimicrobial compounds. And this newest, [INAUDIBLE], that we were just discussing, is the newest and probably the most interesting one.

But you must understand, this is really a modest effort. And from that modest effort, to have 25 compounds of chemical novelty is an indication that a considerably larger number of antibiotics will be discovered from uncultured bacteria.

IRA FLATOW: Mhm. And this first one, what can it combat? What's it good for?

KIM LEWIS: So this targets a large number of our drug resistant pathogens, such as staph aureus, MRSA, which is one of the super bugs.

IRA FLATOW: Sure.

KIM LEWIS: And the strep pneumonia that causes pneumonia and enterococcus faecalis callous that's causes infective endocarditis, with very limited therapeutic options. It's effective against mycobacterium tuberculosis, where we now have some strains of these unpleasant pathogens that are resistant to all available antibiotics.

IRA FLATOW: And how soon can we expect to see this on the market? Or is it really in such an early stage?

KIM LEWIS: Well, so far, we've been able to cure mice of a number of infections. And that's not a bad predictor of efficacy in humans. Although, of course, we have to do a considerable number of additional tests, in more animal models, toxicity, formulation, and so on. We're about two years away from clinical trials. And those trials take about three years.

IRA FLATOW: Well, thank you very much, Dr. Lewis, for taking time to talk with us. We'll be following you.

KIM LEWIS: Thank you, Ira.

IRA FLATOW: Kim Lewis is a professor and director of the Antimicrobial Discovery Center at Northeastern University, in Boston.

CLOSE

Many of today’s commercial antibiotic compounds were first discovered in soil-dwelling microorganisms. In a biological arms race, pathogens have developed resistance to those common antibiotics, leaving fewer options for doctors and patients. Microbiologist Kim Lewis and colleagues report this week in the journal Nature that they’ve been able to grow colonies of previously uncultured microorganisms from the soil, and have harvested from them a new type of antibiotic they call teixobactin—a compound that they say has both broad activity against a variety of gram-positive pathogens and the potential to remain an effective treatment for years to come.

IRA FLATOW: This is "Science Friday." I'm Ira Flatow. Most of the antibiotics we use, today, weren't just dreamed up from nothing. They were discovered somewhere in nature, part of a natural arms race between species of microbes.

First, there was Fleming and penicillin mold, of course, but then a wave of antibiotics that came from bacteria living in the soil. In more recent years, as that well has run dry, researchers have tried designing antibiotics from the ground up, in the lab. That's only been limited, only had a limited success because the bacteria have evolved a resistance to many of the antibiotics on the market.

Going back to the future, scientists have returned to the soil to see if they can find new hope among the 99% of bacteria that refuse to grow in the laboratory. It's an incredible number. You can't grow 99% of the bacteria in a laboratory.

But we now have some hope because they have succeeded in at least one. According to the journal Nature, they've come up with a way to grow some of those unculturable soil bacteria. And when they did, they found what might be the first-- an entirely new class of antibiotics, one that even works against some of the drug resistant strains out there.

Joining me now, to talk about it, is Kim Lewis. He's one of the authors of the report. He's a professor and director of the Antimicrobial Discovery Center at Northeastern University, in Boston. Welcome to the program.

KIM LEWIS: Thanks for having me.

IRA FLATOW: You've been working on this idea for years. Have you not?

KIM LEWIS: Yes. That's true.

IRA FLATOW: And basically, describe what you did. To me, it almost looked like planting tomato seeds in egg shell crates.

KIM LEWIS: It is actually very similar to that. So with my collaborator, Slava Epstein here at Northeastern, we were wondering, how could we figure out a way to grow uncultured bacteria. And it became obvious to us that we're not going to succeed if we continue tinkering with growth media in our Petri dishes because that hasn't worked.

Then we decided that, how about we try growing them in their natural environment, where, of course, they do grow? So we came up with a simple gadget to do that. The gadget is a diffusion chamber.

We take a sample from soil and dilute mix with agar. And instead of pouring it into the Petri dish, we sandwich it between two semipermeable membranes, which then get glued onto an O-ring. And that contraption goes back into the soil.

So now everything diffuses through that chamber. And bacteria get their nutrients and growth factors from the natural environment. And they grow. So essentially, we trick them. They don't know that something happened to them.

IRA FLATOW: And so they grow into a colony which you can, then, take into the lab in a Petri dish.

KIM LEWIS: Yes. Exactly. What we discovered is that once a colony is formed, then, with a high probability, it will become domesticated and will grow in the lab.

IRA FLATOW: Mhm. And what were you able to-- one in particular, one-- you grew 10,000 of these. Right? And you've found one that was exceptional.

KIM LEWIS: Yes. So this is a collaboration, I must say, with NovoBiotic, a startup company here in Cambridge, that is using this technology and collaborating with us. And so, from that collection of strains, we found, of course, a number of bacteria that produce antibiotics. But one was particularly interesting.

It was only distantly related to known organisms. It was unusual in the number of features and was making a potent compound. But there was one very striking feature of that compound that we did not anticipate, did not expect at all. We could not find any resistance to this compound, in the pathogens we tested it against.

IRA FLATOW: Mhm. And this new method, it holds a potential for discovering many, many more antibiotics?

KIM LEWIS: Yes. Of course. So the culture collection that NovoBiotic put together, so far, is 50,000 isolates. From that number, we discovered 25 new antimicrobial compounds. And this newest, [INAUDIBLE], that we were just discussing, is the newest and probably the most interesting one.

But you must understand, this is really a modest effort. And from that modest effort, to have 25 compounds of chemical novelty is an indication that a considerably larger number of antibiotics will be discovered from uncultured bacteria.

IRA FLATOW: Mhm. And this first one, what can it combat? What's it good for?

KIM LEWIS: So this targets a large number of our drug resistant pathogens, such as staph aureus, MRSA, which is one of the super bugs.

IRA FLATOW: Sure.

KIM LEWIS: And the strep pneumonia that causes pneumonia and enterococcus faecalis callous that's causes infective endocarditis, with very limited therapeutic options. It's effective against mycobacterium tuberculosis, where we now have some strains of these unpleasant pathogens that are resistant to all available antibiotics.

IRA FLATOW: And how soon can we expect to see this on the market? Or is it really in such an early stage?

KIM LEWIS: Well, so far, we've been able to cure mice of a number of infections. And that's not a bad predictor of efficacy in humans. Although, of course, we have to do a considerable number of additional tests, in more animal models, toxicity, formulation, and so on. We're about two years away from clinical trials. And those trials take about three years.

IRA FLATOW: Well, thank you very much, Dr. Lewis, for taking time to talk with us. We'll be following you.

KIM LEWIS: Thank you, Ira.

IRA FLATOW: Kim Lewis is a professor and director of the Antimicrobial Discovery Center at Northeastern University, in Boston.